J . Org. Chem. 2001, 66, 633-634
633
Ta ble 1. Regioselective Oxid a tion of Ar ylbor on ic Acid s
to P h en ols
Regioselective Con ver sion of Ar ylbor on ic
Acid s to P h en ols a n d Su bsequ en t Cou p lin g
to Sym m etr ica l Dia r yl Eth er s
J u¨rgen Simon, Stefan Salzbrunn, G. K. Surya Prakash,*
Nicos A. Petasis,* and George A. Olah
Donald P. and Katherine B. Loker Hydrocarbon
Research Institute and Department of Chemistry,
University of Southern California, University Park,
837 West 37th Street, Los Angeles, California 90089-1661
gprakash@usc.edu
Received November 7, 2000
The development of mild methods for the synthesis of
diaryl ethers1 has recently gained increased attention in
several research groups,2-9 mainly due to their important
roles in antibiotics and other biologically active com-
pounds.10,11 Furthermore, poly(aryl ethers) are important
commercial polymers.12 However, synthesis through con-
ventional methods tends to be problematic, especially in
the case of unactivated aromatic substrates. Although
modifications of the classical Ullmann diaryl ether
synthesis13,14 have lead to improvements,5-9 harsh reac-
tion conditions are usually required. For most applica-
tions, milder reaction conditions are desirable. Recently,
Chan and Evans independently reported the copper(II)-
promoted arylation of phenols with arylboronic acids
under mild conditions.2,3
As part of our ongoing research on regioselective
substitutions of arylboronic acids, we have reported the
ipso-halogenation15 and ipso-nitration16 of arylboronic
acids. We now report the conversion of arylboronic acids
to phenols and subsequent coupling to form symmetrical
diaryl ethers in one pot.
Ta ble 2. Effect of H2O2 Ra tio on Over a ll P r od u ct Yield s
Resu lts a n d Discu ssion
In our reaction sequence, we first converted arylboronic
acids to phenols. To the best of our knowledge, there are
H2O2 equivalents
solvent
isolated yield (%)a
0.40
0.15
0.25
0.31
0.40
0.45
H2O/no MS
CH2Cl2/MS
CH2Cl2/MS
CH2Cl2/MS
CH2Cl2/MS
CH2Cl2/MS
-
65
90
61
45
28
(1) For a recent review, see: Theil, F. Angew. Chem. 1999, 111, 2493;
Angew. Chem., Int. Ed. 1999, 38, 2345.
(2) Chan, D. M. T.; Monaco, K. L.; Wang, R.-P.; Winters, M. P.
Tetrahedron Lett. 1998, 39, 2933.
(3) Evans, D. A.; Katz, J . L.; West, T. R. Tetrahedron Lett. 1998,
39, 2937.
(4) Pearson, A. J .; Belmont. P. O. Tetrahedron Lett. 2000, 41, 1671.
(5) Bois-Choussy, M.; Beugelmans, R.; Bouillon, J .; Zhu, J . Tetra-
hedron Lett. 1995, 36, 4781.
a
Based on H2O2 (limiting reagent) employed.
(6) Noda, H.; Niwa, M.; Yamamura, S. Tetrahedron Lett. 1981, 22,
3247.
only few methods described in the literature17-20 for this
transformation. By simply adding an aqueous hydrogen
peroxide solution, we were able to obtain the phenols in
good yields (Table 1) with the desired regioselectivity. A
variety of substituents are tolerated on the aromatic
substrate, and even strongly deactivating substituents
give satisfying results (entry 7).
(7) Evans, D. A.; Barrow, J . C.; Watson, P. S.; Ratz, A. M.; Dinsmore,
C. J .; Evrard, D. A.; DeVries, K. M.; Ellmann, J . A.; Rychnovsky, S.
D.; Lacour, J . J . Am. Chem. Soc. 1977, 119, 3419.
(8) Nicolaou, K. C.; Boddy, C. N. C.; Natarajan, S.; Yue, T.-Y.; Li,
H.; Bra¨se, S.; Ramanjulu, J . M. J . Am. Chem. Soc. 1997, 119, 3421.
(9) Marcoux, J .; Doye, S.; Buchwald, S. J . J . Am. Chem. Soc. 1997,
119, 10539.
(10) Atkinson, B. A. In Antibiotics in Laboratory Medicine; Lorian,
V., Ed.; Williams and Wilkins: Baltimore, 1986; p 995.
(11) Glycopeptide Antibiotics, Drugs and the Pharmaceutical Sci-
ences; Nagarajan, R., Ed.; Decker, Inc.: New York, 1994; Vol. 63.
(12) Labadie, J . W.; Hedrick, J . L.; Ueda, M. Am. Chem. Soc. Symp.
Ser. 1996, 624, 210.
On the basis of these results, we developed a one-pot
coupling sequence for the symmetrical diaryl ethers in
(13) Ullmann, F. Chem. Ber. 1904, 37, 853.
(14) Lindley J . Tetrahedron 1984, 40, 1433.
(15) Thiebes, C.; Prakash, G. K. S.; Petasis, N. A.; Olah, G. A. Synlett
1998, 141.
(17) Hawthorne, M. F. J . Org. Chem. 1957, 22, 1001.
(18) Webb, K. S.; Levy, D. Tetrahedron Lett. 1995, 36, 5117.
(19) Bank, S.; Longley, K. L. J . Labeled Compd. Radiopharm. 1990,
28, 41.
(16) Salzbrunn, S.; Simon, J .; Prakash, G. K. S.; Petasis, N. A.; Olah,
G. A. Synlett 2000, 1485.
(20) Matsui, S.; Takeuchi, H.; Miyasawa, K.; Goto, Y. J P 10025261,
1998.
10.1021/jo0015873 CCC: $20.00 © 2001 American Chemical Society
Published on Web 12/14/2000